Obesity and diabetes are associated with abnormalities in mitochondrial function and biogenesis. Mitochondria are responsible for oxidizing substrates to produce ATP, and for dissipating chemical energy by thermogenesis. Recent work has revealed the surprising discoveries that white adipose tissue can acquire features of brown adipose tissue (beige fat), and that endothelial cells can serve as precursor to adipocytes. There is now significant evidence that NO and eNOS are involved in energy expenditure and insulin sensitivity. Loss of function models show diet-induced obesity and insulin resistance, while gain of function models have the opposite phenotype, with higher metabolic rate and diminished fatty acid oxidation. In addition to the classical respiratory chain, mitochondrial function also involves substrate availability, biogenesis, fission and fusion, cell signaling, programmed cell death, and thermogenesis. The relative effects of NO on these processes may vary between different tissues, both at baseline and in the setting of nutrient excess.
This Frontiers Topic will focus on the roles of NO on mitochondrial biology, and how these roles affect normal physiology and metabolism, and the development of metabolic diseases such as obesity and diabetes. The specific mechanisms of NO action include classical cGMP mediated effects, direct binding of NO to heme, post-translational modifications such as S-nitrosylation, and secondary ROS/RNS species such as peroxynitrite. The specific targets of NO include mitochondrial biogenesis, fission, fusion, and structure; oxidative phosphorylation, glycolysis, and fatty acid oxidation; apoptosis and signaling; thermogenesis and UCP-1 expression; and differentiation of white and brown adipocytes (and related intermediate cell types).
Obesity and diabetes are associated with abnormalities in mitochondrial function and biogenesis. Mitochondria are responsible for oxidizing substrates to produce ATP, and for dissipating chemical energy by thermogenesis. Recent work has revealed the surprising discoveries that white adipose tissue can acquire features of brown adipose tissue (beige fat), and that endothelial cells can serve as precursor to adipocytes. There is now significant evidence that NO and eNOS are involved in energy expenditure and insulin sensitivity. Loss of function models show diet-induced obesity and insulin resistance, while gain of function models have the opposite phenotype, with higher metabolic rate and diminished fatty acid oxidation. In addition to the classical respiratory chain, mitochondrial function also involves substrate availability, biogenesis, fission and fusion, cell signaling, programmed cell death, and thermogenesis. The relative effects of NO on these processes may vary between different tissues, both at baseline and in the setting of nutrient excess.
This Frontiers Topic will focus on the roles of NO on mitochondrial biology, and how these roles affect normal physiology and metabolism, and the development of metabolic diseases such as obesity and diabetes. The specific mechanisms of NO action include classical cGMP mediated effects, direct binding of NO to heme, post-translational modifications such as S-nitrosylation, and secondary ROS/RNS species such as peroxynitrite. The specific targets of NO include mitochondrial biogenesis, fission, fusion, and structure; oxidative phosphorylation, glycolysis, and fatty acid oxidation; apoptosis and signaling; thermogenesis and UCP-1 expression; and differentiation of white and brown adipocytes (and related intermediate cell types).
